Nephrolithiasis or urolithiasis is a common disorder defined as the development of stones within the urinary tract such as the kidney stone disease. This disorder represents a serious health problem. Depending on local conditions, between 1 and 14% of the population suffers from this condition. The economic impact of urolithiasis in the U.S. was estimated to be $1.83 billion in 1993 (Grases, et al., International Urology and Nephrology, 31(5) pp. 591–600 (1999)). Current preventative/treatment for urolithiasis are not easy to take and not that effective, e.g., potassium citrate tablets.
Calcium oxalate is the dominant component in kidney stones. The amount of oxalate excreted in urine has a significant impact on calcium oxalate supersaturation and kidney stone formation (R. Holmes, et al., Kidney International, 59, pp. 270–276 (2001)). In addition, calcium oxalate is also known to be associated with arthritis (Reginato A J, Kumik B R C: “Calcium oxalate and other crystals associated with kidney disease and arthritis,” Semin Arthirtis Rheum 18:198, 1989).
PCT publication WO 99/22744 suggests the use of aliphatic polyamines to reduce the levels of oxalate in the digestive tract. This publication suggests that the polyamines be administered orally optionally in the presence of enzymes, such as oxalate decarboxylase or oxalate oxidase which can decompose oxalate. Various forms of oral dosage are described. The contents of this publication are incorporated herein by reference.
Hydrates of lanthanum carbonate [La2(CO3)3] are described in U.S. Pat. No. 5,968,976 and WO 96/30029 for treating hyperphosphataemia in patients with renal failure by removing elevated levels of phosphates. This treatment is especially useful in patients undergoing kidney dialysis. These compounds are particularly preferred.
There exists a need for agents that bind oxalate and thereby inhibit or prevent stone formation in the kidneys. The present invention addresses this need by using rare earth compounds to lower levels of oxalate in animals, including humans.
Citation of the above documents is not intended as an admission that any of the foregoing is pertinent prior art. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents. Further, all documents referred to throughout this application are hereby incorporated in their entirety by reference herein.